Hemostatic Agents: Cost-Effectiveness Issues

1. Hemostatic Agents: Cost-Effectiveness Issues Peter K. Smith, MD Professor and Chief Thoracic Surgery Duke University

2. Tranexamic RCT Cardiac Surgery (n=163) 10 mg/kg (incision)  1 mg/kg/hr Horrow et al. Circulation 1991; 84:2063

3. Aprotinin vs EACA Efficacy - Demographics Bennett-Guerrero et al. Anesthesiology 1997;87:1373

4. Aprotinin vs EACA: Efficacy Bennett-Guerrero et al. Anesthesiology 1997;87:1373

5. Test Dose Loading Dose Pump-Prime Dose 1 ml 200 ml 200 ml Bypass Period Operation Period Constant Infusion 50 ml / h High-Dose Aprotinin Original Administration Regimen Royston et al Lancet 1987 Dec 5;2:1289-91

6. Aprotinin Dosing Mossinger et al, ATS 1998;65:S45-51

7. Aprotinin Dosing • Half-dose FDA Regimen B • 1 ml (10,000 KIU) test dose • 100 ml (1,000,000 KIU) loading dose • 100 ml (1,000,000 KIU) pump prime • 25 ml (250,000 KIU) per hour CPB

8. Aprotinin Dosing Mossinger et al, ATS 1998;65:S45-51

9. Aprotinin Effect on Survival

10. Aprotinin and Myocardial Infarction

11. Aprotinin and Stroke Incidence * *

12. Cost of Therapy • Drug cost • Cost of storage and administration • Indirect costs • Cost of complications related to the drug • In-Hospital • Lifetime

13. Cost Savings • Reduction of blood products and their complications • Reduced OR time and incidence of return • Reduction of inflammatory syndrome • Reduction of complications related to the drug • Cardiac team satisfaction • Patient satisfaction

14. Aprotinin vs EACA - Efficacy/Cost • Prospective randomized double-blind trial • Repeat median sternotomy- CABG, valve, or both • n= 204 • High dose EACA or Aprotinin (on incision) • Efficacy analysis • Cost/benefit analysis (bleeding related costs) Bennett-Guerrero et al. Anesthesiology 1997;87:1373

15. Aprotinin vs EACA Cost/Benefit • Perspective of the hospital • Bleeding related costs (not charges), e.g. drug, direct & indirect blood product costs, OR time • No differences in other outcomes expected or seen • Costs Aprotinin Rx higher ($1,813 vs $1,088*) • Sensitivity analysis w/ half dose aprotinin- no chg • Threshold value for aprotinin = $486 Bennett-Guerrero et al. Anesthesiology 1997;87:1373

16. Lifetime Cost of Therapy • Myocardial Infarction Lifetime Costs • ~$25,000 more than matched (age, gender) patients without MI • With an incidence of 1%, 1 of 100 patients would generate $25,000 in total cost; or • $250 per patient per percent MI change • Stroke Lifetime Costs • ~$100,000 more than matched patients without stroke • With an incidence of 1%, 1 of 100 patients would generate $100,000 total cost; or • $1000 per patient per percent stroke change

17. Cost Effectiveness of Aprotinin • Drug cost is dose dependent and linear • Effects are dose dependent and non-linear • Effects are only well known at the three doses tested in double-blind trials

18. 8 y = -2.940LOG(x) + 9.802 6 4 Given (Units) Hemostatic Factors 2 0 0 250 500 750 1000 Total Dose of Aprotinin (mg) Aprotinin Dose vs Hemostatic Factors Given Data from US Multicenter Studies for Repeat CABG Surgery

19. 8 6 4 Given (Units) Hemostatic Factors 2 0 0 250 500 750 1000 Total Dose of Aprotinin (mg) Aprotinin Dose vs Hemostatic Factors vs Cost $1200 $600 Data from US Multicenter Studies for Repeat CABG Surgery

20. 8 6 4 Given (Units) Hemostatic Factors 2 0 0 250 500 750 1000 Total Dose of Aprotinin (mg) Aprotinin Dose vs Definite MI 10% 5% Data from US Multicenter Studies for All CABG Surgery

21. 8 6 4 Given (Units) Hemostatic Factors 2 0 0 250 500 750 1000 Total Dose of Aprotinin (mg) Aprotinin Dose vs Mortality 5% 2.5% Data from US Multicenter Studies for All CABG Surgery

22. 8 6 4 Given (Units) Hemostatic Factors 2 0 0 250 500 750 1000 Total Dose of Aprotinin (mg) Aprotinin Dose vs Stroke Outcome 3% 2% 1% Data from US Multicenter Studies for All CABG Surgery

23. Randomized Trial Analysis • Resources used (OR time, blood tx, ICU LOS, Total LOS, etc, etc) as well as age, gender and complication rate were analyzed from the randomized patients. • Model developed on Duke 1300 CABG patients with same resources related multivariably to actual cost. • Adjusted model R2=0.74

25. Randomized Trial Composition

26. Cost Model Coefficients

27. Itemized Resources-Primary CABG

28. Complications-Primary CABG

29. Randomized Trial Resource Use Data: Primary CABG Transformed to Cost Through Duke Data Model

30. Cost-Primary CABG

31. Itemized Resources-Redo CABG

32. Complications-Redo CABG

33. Repeat CABG Peri-operative Costs Full Dose Half Dose Placebo Mean CABG Cost Subtotal $27,458† $28,086† $30,910 (Difference from placebo) ($3,452) ($2,825) -- Aprotinin Cost $1,394 $703 -- Total Peri-op. Cost $28,852† $28,789† $30,910 (Difference from placebo) ($2,058) ($2,122) -- Lifetime Stroke Complication $508† $1,295† $4,444 Lifetime AMI Complication $3,351 $4,188 $3,401 Total Lifetime Costs $32,711† $34,272† $38,755 (Difference from Placebo) ($6,044) ($4,483) -- Randomized Trial Resource Use Data: Redo CABG Transformed to Cost Through Duke Data Model

34. Cost-Redo CABG